How the Brain Deletes Old Memories

Do you remember your first birthday? How about what you ate for breakfast weeks ago? For most people, such events slip through the sieve of memory, never to be retrieved. Now, the first study of its kind in mice suggests that the brain may clear away that old information in the process of forming new memories.

For the most part, the brain stops producing new neurons—a process called neurogenesis—soon after birth. In humans, mice, and some other species, however, neurogenesis continues throughout life in a brain region that encodes memories about space and events, called the dentate gyrus of the hippocampus. In adult humans, the dentate gyrus produces roughly 700 new brain cells each day.

Studies in mice have shown that suppressing neurogenesis can impair a type of learning called pattern separation, which allows us to distinguish between two similar but slightly different circumstances. One example is remembering where you parked the car from 1 day to the next, explains René Hen, a neuroscientist at Columbia University who was not involved in the new study.

Although the precise role of neurogenesis in memory is still controversial, more than a decade of research has demonstrated that boosting neurogenesis with exercise and antidepressants such as Prozac can increase rodents' ability to learn new information about places and events. A few years ago, however, neuroscientist Paul Frankland of the Hospital for Sick Children in Toronto, Canada, noticed that some of the animals in his experiment actually did worse on certain memory tasks when their neuron birth rates had been ramped up. In particular, they performed poorly on tests that required them to retain details about past events.

The result was “way too interesting to ignore,” Frankland says. Because neurogenesis surges in newborn mice and humans and then tapers to a slow trickle by adulthood, Frankland and colleagues wondered if that explosion of new neurons could help explain the widespread phenomenon of infantile amnesia—the inability of adults to remember events that occurred before they were 2 to 4 years old. Some theoretical models suggested that new neurons destabilize memories already stored in the hippocampus by degrading the information there, but the idea had never been explored in live animals.

To test the hypothesis, Frankland and his team first compared the stability of memories in adult mice versus 17-day-old mice, which are equivalent to human babies less than a year old. They removed the rodents from their familiar, sawdust-lined enclosures and put them into a box with a metal floor that delivered brief foot shocks. After returning the mice to their cages, over the course of 6 weeks the researchers placed the rodents back in the box but did not repeat the shocks. More than a month later, the adult mice continued to freeze when placed in the environment where they'd had the painful experience. The younger mice, however, forgot the association within a day. The juveniles "can remember for 24 hours, but then they forget," Frankland says.

Next, the team looked at whether different rates of neurogenesis between adult and infant mice could explain the young rodents' forgetfulness. Exercise can increase neurogenesis in mice by more than 50%, so the researchers gave a separate group of adult mice wheels to run in. (Left to their own devices, mice will run up to 5 kilometers a night.) They also treated separate groups of mice with drugs, such as Prozac, that boost new neuron birth. Increasing neurogenesis by as much as 100% returned the adult mice to an "infantlike" state of forgetfulness in the foot shock test and other similar memory tasks, Frankland and his colleagues report online today in Science.

It is difficult to completely eliminate the birth of new neurons in infant mice, but by genetically engineering dividing neural stem cells to self-destruct the team was able to achieve about a 50% reduction of neurogenesis in the animals, Frankland says. With less neurogenesis, the young rodents acted more like adult mice in the experiment. They froze when first placed in the box for roughly a week, rather than just 1 day, after receiving the foot shocks.

Psychologists have long considered the process of forgetting as key to a healthy mind, yet neuroscientists haven’t paid much attention to it in the past, Frankland says. "If you embrace the idea that forgetting is healthy," then it makes sense that neurogenesis may contribute to the clearing out of old memories, he says. Although it's pure speculation at this point, he says, it's possible that one way that antidepressants help people with depression, a condition linked to reduced neurogenesis, "is to promote some sort of clearing or forgetting," he says.

"One has to be a bit cautious" about extrapolating the new findings to people because we don’t have a way to measure neurogenesis in the live human brain, Hen notes. Forgetting may also be a downside of adult neurogenesis because the new memories outcompete old memories, notes neuroscientist Jonas Frisén of the Karolinska Institute in Stockholm. “This is an exciting new insight.”